Pre-synaptic and post-synaptic development in the central nervous system will be studied using cultures of mouse brain. The objectives of this project are to define: 1) any interrelations between pre- and post-synaptic elements; and 2) any effects of drugs of abuse on these elements. Pre-synaptic development will be studied following the development of 1) enzymes that synthesize acetylcholine, gamma-amino butyric acid and catecholamines and 2) systems that transport monoamine neurotransmitters. Post-synaptic development will be studied by determining the development of receptors for acetylcholine (muscarinic), gamma-amino butyric acid, glycine, serotonin, and opiates as measured by binding of radioactively labelled quinuclidinyl benzilate (QNB), gamma-amino butyric acid, strychnine, d-LSD and naloxone, respectively. By studying this development when cells are chronically grown in the presence of certain drugs of abuse, the effects of these agents on pre-and post-synaptic development will be determined.